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ClinicalTrials.gov ID

NCT07665788

Lead Sponsor

University Hospital, ToursOTHER

Overall Status

Not yet recruiting

Study Type

Interventional

Phase

Phase 3

Enrollment

250Estimated

Last Update Posted

Jun 24, 2026Actual

Start Date

Jun 1, 2026Estimated

Primary Completion Date

Jul 1, 2029Estimated

Completion Date

Sep 1, 2029Estimated

Official Title

A Multicentre, Double-blind, Randomized Controlled Trial of Inhaled Amikacin Versus Placebo in Critically Ill Patients With Ventilator-associated Tracheobronchitis

Brief Summary

The primary objective of the AMIVAT trial is to assess whether a 5-day course of inhaled amikacin, compared to placebo, reduces the incidence of progression to ventilator-associated pneumonia (VAP) at day 28 in intensive care unit (ICU) patients with ventilator-associated tracheobronchitis (VAT). Transition from VAT to VAP will be defined as the occurrence of a first VAP episode due to the same pathogens than those responsible for VAT.

Detailed Description

VAT will be defined using the following criteria: (i) duration of mechanical ventilation > 48 hours, (ii) purulent tracheobronchial secretions, (iii) no new or progressive persistent pulmonary infiltrate on chest X-ray, and (iv) bacterial growth on endotracheal aspirate (ETA) ≥10.5 colony-forming unit (CFU)/mL or on bronchoalveolar lavage ≥10.4 CFU/mL or on plugging telescopic catheter ≥10.3 CFU/mL. Inclusion and randomization will be performed after written informed consent, as soon as inclusion criteria are met, within 24 hours after VAT suspicion (ETA sampling) whenever possible. Patients in the experimental group will receive inhaled amikacin (once daily, 20 mg/kg of predicted body weight with a maximum of 2 grams) from Day 1 (inclusion, randomization and first nebulization) to Day 5 through an optimized and protocolized nebulization procedure (vibrating mesh nebulizer). Patients in the control group will receive inhaled placebo (NaCl 0.9%, once daily) from Day 1 (inclusion, randomization and first nebulization) to Day 5 through an optimized and protocolized nebulization procedure (vibrating mesh nebulizer). Nebulization will be performed according to a standardized procedure using a vibrating mesh nebulizer (Aerogen Solo, Aerogen, Galway, Ireland). A bedside checklist will be used to ensure optimal implementation practice. All staff involved in nebulization will be trained prior to their study involvement. The systemic diffusion and pharmacokinetics of inhaled amikacin will be assessed through measurement of peak and residual blood concentrations in a pre-planned subsample of patients. Study treatment will be discontinued before the 5th administration in the following cases: (i) documented acquired amikacin resistance in at least one pathogen responsible for VAT, (ii) occurrence of VAP before Day 5, (iii) occurrence of AKI stage 2 or 3 of the KDIGO classification before Day 5 (except for patients receiving renal replacement therapy), (iv) clinical indication for mandatory IV aminoglycoside therapy (amikacin, gentamicin, tobramycin) before Day 5, (v) extubation before Day 5, (vi) unexpected SAE deemed related to the IP and/or a patient's clinical condition that requires suspension of the treatment according to the local investigator. Patients will be followed-up until Day 28 for the primary study endpoint and up to Day 90 for certain secondary study endpoints (Day-90 mortality, and day-90 health-related quality of life [HRQoL] in survivors).

• Ventilator-Associated Pneumonia
• Ventilator-Associated Tracheobronchitis

• Optimized and protocolized nebulization procedure.

Ages Eligible for Study

Adult (18-64)Older Adult (65+)

Sexes Eligible for Study

All

Accepts Healthy Volunteers

No

Eligibility Criteria

Inclusion criteria:

• Age ≥ 18 years
• Admission to a participating intensive care unit (ICU)
• Invasive mechanical ventilation > 48 hours
• First episode of ventilator-associated tracheobronchitis during the ICU stay defined using the following criteria: (i) purulent tracheobronchial secretions, (iii) no new or progressive persistent pulmonary infiltrate on chest X-ray, and (iv) bacterial growth on endotracheal aspirate ≥10.5 colony-forming unit (CFU)/mL or on bronchoalveolar lavage ≥10.4 CFU/mL or on plugging telescopic catheter ≥10.3 CFU/mL
• Coverage by the French health insurance system (Social Security)
• Written informed consent obtained from the patient, or, if the patient is not able to give written consent, from his or her legally designated representative (trusted person designated by the patient or, failing that, a family member) or, failing that, inclusion performed by the investigator within the therapeutic window (in such cases, informed consent will be sought by the investigator from the patient, or his or her legally designated representative, whichever is sooner). In all cases, the patient's written informed consent will be obtained as soon as possible.
• For woman of childbearing potential: negative pregnancy test result at the time of inclusion

Exclusion criteria:

• Previous ventilator-associated pneumonia due to the pathogens responsible for ventilator-associated tracheobronchitis during the same ICU stay
• On-going antimicrobial therapy fpr ventilator-associated pneumonia
• Ventilator-associated tracheobronchitis due to pathogens with intrinsic amikacin resistance (e.g. Stenotrophomonas maltophilia)
• On-going therapy with intravenous amikacin or another aminoglycoside
• Acute kidney injury stage 2 or 3 of the Kidney Disease Improving Global Outcomes (KDIGO) classification and/or advanced chronic kidney failure (glomerular filtration rate <30 mL/min), except in patients under renal replacement therapy
• Grade B or C cirrhosis (Child-Pugh classification)
• Scheduled extubation within 24h
• Prior tracheotomy
• Administration of inhaled antibiotics within the 7 preceding days
• Known hypersensitivity to amikacin, another aminoglycoside, or any of the excipients
• Myasthenia gravis
• Contraindication to nebulization
• On-going treatment with ataluren
• Persons covered by articles L1121-5 to L1121-8 of the French Public Health Code (corresponding to all protected persons: pregnant women, parturients, nursing mothers, persons deprived of their liberty by judicial or administrative decision, minors, and persons subject to a legal protection measure: guardianship or trusteeship).
• Moribund patient
• End-of-life decision
• Previous inclusion in the present study
• Participation to another interventional study
• Inability of the patient, or the person providing consent, to understand all aspects of the research
• Patient being a relative of the investigator or a relative of someone from the team directly involved in the trial, including doctors and pharmacists

Primary Purpose

Treatment

Allocation

Randomized

Interventional Model

Parallel Assignment

Masking

Quadruple

Lead Sponsor

University Hospital, ToursOTHER

Collaborators

AerogenINDUSTRY

grouilj@ch-blois.fr02 54 55 60 73

jean-francois.timsit@aphp.fr01 40 25 77 03